title: A novel mitochondrial DNA point mutation in the tRNA(Ile) gene: studies in a patient presenting with chronic progressive external ophthalmoplegia and multiple sclerosis.
abstract: We report a new mutation, a G to A transition at nucleotide position 4298 within the mitochondrial tRNA(Ile) gene in a patient with chronic progressive external ophthalmoplegia and multiple sclerosis. The mutation, which alters an evolutionary conserved nucleotide within the anticodon stem, was heteroplasmic in skeletal muscle but was not present in the patient's blood. Single fibre PCR analysis revealed significantly higher levels of the G4298A mutation in cytochrome c oxidase (COX) negative fibres than in COX-positive fibres. This mutation represents the seventh pathogenic nucleotide substitution to be found in this gene and as such confirms the tRNA(Ile) gene as a susceptible "hot spot" for mitochondrial DNA point mutations. Of particular interest is that this patient has the clinical features of both multiple sclerosis and a mitochondrial DNA disorder.
authors.affiliation: Department of Neurology, Medical School, University of Newcastle upon Tyne, United Kingdom.
authors.forename: R W
authors.initials: RW
authors.lastname: Taylor
authors.forename: P F
authors.initials: PF
authors.lastname: Chinnery
authors.forename: M J
authors.initials: MJ
authors.lastname: Bates
authors.forename: M J
authors.initials: MJ
authors.lastname: Jackson
authors.forename: M A
authors.initials: MA
authors.lastname: Johnson
authors.forename: R M
authors.initials: RM
authors.lastname: Andrews
authors.forename: D M
authors.initials: DM
authors.lastname: Turnbull
mesh_terms: D000818:Animals; D001483:Base Sequence; D004272:DNA, Mitochondrial / Q000737:chemistry / Q000235:genetics*; D003576:Electron Transport Complex IV / Q000378:metabolism; D005260:Female; D006801:Humans; D008875:Middle Aged; D017240:Mitochondrial Myopathies / Q000150:complications / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D009103:Multiple Sclerosis / Q000150:complications* / Q000235:genetics* / Q000378:metabolism; D018485:Muscle Fibers, Skeletal / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism; D009690:Nucleic Acid Conformation; D017246:Ophthalmoplegia, Chronic Progressive External / Q000150:complications* / Q000235:genetics* / Q000378:metabolism; D017354:Point Mutation; D012355:RNA, Transfer, Ile / Q000235:genetics*; D012689:Sequence Homology, Nucleic Acid; D013045:Species Specificity
chemical_list: D004272:DNA, Mitochondrial; D012355:RNA, Transfer, Ile; D003576:Electron Transport Complex IV